6-Hydroxy dopamine does not affect lens-induced refractive errors but suppresses deprivation myopia

Schaeffel, Frank; Hagel, Gabi; Bartmann, Marieluise; Köhler, Konrad; Zrenner, Eberhart

doi:10.1016/0042-6989(94)90327-1

Cited by 97 publications

(56 citation statements)

References 12 publications

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“…Pirenzepine, however, is effective at inhibiting chick FDM, possibly due to binding to the cM 2 receptor, which MT7 does not recognize, or to off-target binding at a 2 -adrenoceptors as evidenced by our work. These differences in treatment effectiveness of mamba toxins are in line with evidence suggesting that the circuits involved in LIM and FDM are in some ways different, [120][121][122] and thatwhatever the mechanism affected by atropine (and other myopia-inhibiting mAChR antagonists) is-the results of our study may be unique to the circuitry of FDM, and not LIM.…”

Section: Caveats and Considerationssupporting

confidence: 77%

Myopia-Inhibiting Concentrations of Muscarinic Receptor Antagonists Block Activation of Alpha_2A-Adrenoceptors In Vitro

Carr

Mihara

Ramachandran

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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Citation: Carr BJ, Mihara K, Ramachandran R, et al. Myopia-inhibiting concentrations of muscarinic receptor antagonists block activation of alpha 2A -adrenoceptors in vitro. Invest Ophthalmol Vis Sci. 2018;59:2778-2791. https://doi.org/10.1167 PURPOSE. Myopia is a refractive disorder that degrades vision. It can be treated with atropine, a muscarinic acetylcholine receptor (mAChR) antagonist, but the mechanism is unknown. Atropine may block a-adrenoceptors at concentrations ‡0.1 mM, and another potent myopiainhibiting ligand, mamba toxin-3 (MT3), binds equally well to human mAChR M 4 and a 1A -and a 2A -adrenoceptors. We hypothesized that mAChR antagonists could inhibit myopia via a 2A -adrenoceptors, rather than mAChR M 4 . METHODS.Human mAChR M 4 (M 4 ), chicken mAChR M 4 (cM 4 ), or human a 2A -adrenergic receptor (hADRA2A) clones were cotransfected with CRE/promoter-luciferase (CRE-Luc; agonist-induced luminescence) and Renilla luciferase (RLuc; normalizing control) into human cells. Inhibition of normalized agonist-induced luminescence by antagonists (ATR: atropine; MT3; HIM: himbacine; PRZ: pirenzepine; TRP: tropicamide; OXY: oxyphenonium; QNB: 3-quinuclidinyl benzilate; DIC: dicyclomine; MEP: mepenzolate) was measured using the DualGlo Luciferase Assay System. RESULTS.Relative inhibitory potencies of mAChR antagonists at mAChR M 4 /cM 4 , from most to least potent, were QNB > OXY ‡ ATR > MEP > HIM > DIC > PRZ > TRP. MT3 was 563 less potent at cM 4 than at M 4 . Relative potencies of mAChR antagonists at hADRA2A, from most to least potent, were MT3 > HIM > ATR > OXY > PRZ > TRP > QNB > MEP; DIC did not antagonize.CONCLUSIONS. Muscarinic antagonists block hADRA2A signaling at concentrations comparable to those used to inhibit chick myopia ( ‡0.1 mM) in vivo. Relative potencies at hADRA2A, but not M 4 /cM 4 , correlate with reported abilities to inhibit chick form-deprivation myopia. mAChR antagonists might inhibit myopia via a 2 -adrenoceptors, instead of through the mAChR M 4 /cM 4 receptor subtype.

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Section: Caveats and Considerationssupporting

confidence: 77%

Myopia-Inhibiting Concentrations of Muscarinic Receptor Antagonists Block Activation of Alpha_2A-Adrenoceptors In Vitro

Carr

Mihara

Ramachandran

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…The relationship between retinal dopamine pathways and lens-induced myopia is less certain. At dosages sufficient to suppress form-deprivation myopia in chicks, development of lens-induced myopia was not suppressed by intra-vitreal injections of 6-hydroxy dopamine, a drug which inhibits dopaminergic pathways (Schaeffel, Hagel et al 1994). Conversely the non-specific dopaminergic agonist apomorphine has been shown to block negative lens-induced myopia in other chick studies (Schmid and Wildsoet 2004;Nickla, Totonelly et al 2010).…”

Section: Dopamine Melatonin and Refractive Development 61 Dopaminementioning

confidence: 89%

Myopia, Light and Circadian Rhythms

Phillips¹,

Backhouse²,

Collins³

2012

Advances in Ophthalmology

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“…Bartmann et al [23] reported that when the chicks were raised in constant light, the development of deprivation myopia was blocked. Weiss and Schaeffel [24] and Schaeffel et al [25] reported that a normal light cycle in relation to the retinal dopamine levels was necessary to develop depri vation myopia. Our results support their view that a diurnal growth rhythm is necessary for the development o f depriva tion myopia.…”

Section: Discussionmentioning

confidence: 99%

“…The degree of visual deprivation-in duced myopia by either lid suture [1][2][3] or goggles [14,15,17,19] varies to a great extent, and the relation between the degree of myopia and the quality of visual deprivation [9] is not well understood. The influence of light and dark envi ronments to visual deprivation-induced myopia [2,15,[20][21][22][23][24][25]] also remains to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Visual Deprivation Myopia with Translucent and Black Goggles

Yoshino

Funata²,

Akazawa³

et al. 1997

Ophthalmologica

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To study how different visual deprivation conditions influence the degree of myopia, chicks were reared under conditions of unilateral and bilateral visual deprivation with translucent and black goggles in environments of a 12-hour light/dark cycle and complete darkness. Two weeks after hatching, the refractive errors and axial lengths of the eyes were measured. The deprived eyes of the light/dark-reared chicks exhibited severe myopia both unilaterally and bilaterally as well as axial elongations. The dark-reared chicks exhibited slight myopia in the eyes with goggles and no significant axial elongation. The experiments suggest that different degrees of visual deprivation can also cause severe myopia, that myopia develops independently in each eye, and that a light/dark environment is required for severe myopia to develop.

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6-Hydroxy dopamine does not affect lens-induced refractive errors but suppresses deprivation myopia

Cited by 97 publications

References 12 publications

Myopia-Inhibiting Concentrations of Muscarinic Receptor Antagonists Block Activation of Alpha_2A-Adrenoceptors In Vitro

Myopia-Inhibiting Concentrations of Muscarinic Receptor Antagonists Block Activation of Alpha_2A-Adrenoceptors In Vitro

Myopia, Light and Circadian Rhythms

Visual Deprivation Myopia with Translucent and Black Goggles

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6-Hydroxy dopamine does not affect lens-induced refractive errors but suppresses deprivation myopia

Cited by 97 publications

References 12 publications

Myopia-Inhibiting Concentrations of Muscarinic Receptor Antagonists Block Activation of Alpha2A-Adrenoceptors In Vitro

Myopia-Inhibiting Concentrations of Muscarinic Receptor Antagonists Block Activation of Alpha2A-Adrenoceptors In Vitro

Myopia, Light and Circadian Rhythms

Visual Deprivation Myopia with Translucent and Black Goggles

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Product

Resources

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Myopia-Inhibiting Concentrations of Muscarinic Receptor Antagonists Block Activation of Alpha_2A-Adrenoceptors In Vitro

Myopia-Inhibiting Concentrations of Muscarinic Receptor Antagonists Block Activation of Alpha_2A-Adrenoceptors In Vitro